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Author Notes:

Correspondence to: Chia-Yi Kuan E-mail: alex.kuan@emory.edu

We thank all collaborators who contributed to our research articles that the present methodology report is based upon.

Disclosures - none.


Research Funding:

This study was supported by the NIH grant NS074559 (to C. K.).


  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • Medicine
  • Issue 102
  • Tissue plasminogen activator (tPA)
  • Laser speckle contrast imaging
  • Thrombosis
  • Virchow's triad
  • Edaravone
  • Reperfusion
  • No-Reflow

A Thrombotic Stroke Model Based On Transient Cerebral Hypoxia-ischemia


Journal Title:

Journal of Visualized Experiments


Volume 2015, Number 102


, Pages e52978-e52978

Type of Work:

Article | Final Publisher PDF


Stroke research has endured many setbacks in translating neuroprotective therapies into clinical practice. In contrast, the real-world therapy (tPA thrombolysis) rarely produces benefits in mechanical occlusion-based experimental models, which dominate preclinical stroke research. This split between the bench and bedside suggests the need to employ tPA-responsive models in preclinical stroke research. To this end, a simple and tPA-reactive thrombotic stroke model is invented and described here. This model consists of transient occlusion of the unilateral common carotid artery and delivery of 7.5% oxygen through a face mask in adult mice for 30 min, while maintaining the animal rectal temperature at 37.5 ± 0.5 °C. Although reversible ligation of the unilateral carotid artery or hypoxia each suppressed cerebral blood flow only transiently, the combination of both insults caused lasting reperfusion deficits, fibrin and platelet deposition, and large infarct in the middle cerebral arterysupplied territory. Importantly, tail-vein injection of recombinant tPA at 0.5, 1, or 4 hr post-tHI (10 mg/kg) provided time-dependent reduction of the mortality rate and infarct size. This new stroke model is simple and can be standardized across laboratories to compare experimental results. Further, it induces thrombosis without craniectomy or introducing pre-formed emboli. Given these unique merits, the tHI model is a useful addition to the repertoire of preclinical stroke research.

Copyright information:

© 2015 Journal of Visualized Experiments.

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